PIK3C3 phosphoinositide-3-kinase, class 3 [Homo sapiens] - Gene

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Summary

Official Symbol: PIK3C3provided by HGNC
Official Full Name: phosphoinositide-3-kinase, class 3provided by HGNC
Primary source: HGNC:8974
See related: Ensembl:ENSG00000078142; HPRD:04009; MIM:602609; Vega:OTTHUMG00000132593
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: VPS34; hVps34; MGC61518

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Genomic context

Location :: 18q12.3

Sequence :: Chromosome: 18; NC_000018.9 (39535199..39661448)

See PIK3C3 in Epigenomics, MapViewer

Chromosome 18 - NC_000018.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway
Title: Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway.
Though dispensable for autophagy induction, transgenic Vps34 is a critical regulator of naive T cell homeostasis, modulating interleukin (IL)-7 receptor alpha trafficking, signaling, and recycling.
Title: The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.
Pik3c3 is essential for central nervous system neuronal homeostasis and Pik3c3 deletion; CaMKII-Cre transgenic mouse is a useful model for studying pathological changes in progressive forebrain neurodegeneration.
Title: Pik3c3 deletion in pyramidal neurons results in loss of synapses, extensive gliosis and progressive neurodegeneration.
Coimmunoprecipitation assay indicated that hepatitis C virus NS4B formed a complex with human Rab5 and Vps34, supporting the notion that Rab5 and Vps34 are involved in NS4B-induced autophagy.
Title: Rab5 and class III phosphoinositide 3-kinase Vps34 are involved in hepatitis C virus NS4B-induced autophagy.
Activation of mTOR by leucine or insulin upregulated hVps34.
Title: The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes.
14-3-3zeta proteins are shown as a negative regulator of autophagy through regulation of a key component of early stages of the autophagy pathway, such as hVps34.
Title: Regulation of autophagic activity by 14-3-3ζ proteins associated with class III phosphatidylinositol-3-kinase.
a critical role of the Rubicon RUN domain in PI3KC3 and autophagy regulation
Title: The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression.
A specific sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates both receptor degradation and cytokinesis, whereas ATG14L, a PI3K-III subunit involved in autophagy, is not required.
Title: A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic.
A PIK3C3 promoter variant (rs3813065/-442 C/T) in an independent multiancestral cohort of 478 systemic lupus erythematosus cases and 522 controls, was examined.
Title: Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients.
Data show that knockdown of Vps34 reduces gossypol-induced autophagy in both MCF-7 human breast adenocarcinoma and HeLa cell lines.
Title: The Bcl-2 homology domain 3 mimetic gossypol induces both Beclin 1-dependent and Beclin 1-independent cytoprotective autophagy in cancer cells.

Submit: New GeneRIF Correction See all (28)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-induced TNF-alpha production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways	PubMed
	env	CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway	PubMed
	env	Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways	PubMed
	env	HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 disrupts the association between phospholipase C gamma-1 and phosphoinositide 3 kinase (PI3-kinase), and this effect is dependent on PI3-kinase activity	PubMed
	env	PI3-kinase activation induced by HIV-1 gp160 leads to downregulation of LFA-1-mediated T cell adhesion to B cells	PubMed
Tat	tat	Pro-survival effects of intracellular HIV-1 Tat in a microglial cell line is attributed to activation of the PI-3-kinase (PI3K)/Akt pathway via decreasing expression of PTEN, a negative regulator of the PI-3-K pathway	PubMed
	tat	HIV-1 Tat activates phosphatidylinositol 3-kinase (PI3K), leading to the activation of Akt/PKB, decreased levels of cAMP and CREB phosphorylation, and the protection of cells from apoptosis	PubMed
	tat	Phosphatidylinositol 3-kinase inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter by affecting the formation of the Tat-associated kinase transactivating complex	PubMed
	tat	HIV-1 Tat induced release of MCP-1 from human lung microvascular endothelial cells involves an interaction between Tat and PI3 kinase	PubMed
	tat	Activation of protein kinase C-epsilon by HIV-1 Tat involves an interaction with PI 3-kinase	PubMed
	tat	HIV-1 Tat-mediated cytopathic changes in human brain microvascular endothelial cells involves its interaction with phosphatidylinositol 3-kinase (PI3K)	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
Q8NEB9	Calmodulin 1	CALM1	HPRD	PubMed
Q8NEB9	Q99570	PIK3R4	HPRD	PubMed
Q8NEB9	Q00169	PITPNA	HPRD	PubMed
Q8NEB9	P61981	YWHAG	HPRD	PubMed
BioGRID:111307	BioGRID:116531	ATG14	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:114226	BECN1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:123354	CLPTM1L	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:115062	KIAA0226	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:107330	KRIT1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:111307	BioGRID:136855	MAP1LC3C	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:119009	NRBF2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:119059	PIK3R4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:111806	RAB5A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:113866	USP11	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:113248	UVRAG	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111307	BioGRID:113364	YWHAG	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
1-phosphatidylinositol-3-kinase activity	IMP Inferred from Mutant Phenotype more info
ATP binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info
protein kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
autophagic vacuole assembly	IEA Inferred from Electronic Annotation more info
cell cycle	IEA Inferred from Electronic Annotation more info
cytokinesis	IMP Inferred from Mutant Phenotype more info
early endosome to late endosome transport	IMP Inferred from Mutant Phenotype more info	PubMed
endosome organization	IEA Inferred from Electronic Annotation more info
innate immune response	TAS Traceable Author Statement more info
insulin receptor signaling pathway	TAS Traceable Author Statement more info
phosphatidylinositol-3-phosphate biosynthetic process	IMP Inferred from Mutant Phenotype more info
phosphatidylinositol-3-phosphate biosynthetic process	TAS Traceable Author Statement more info	PubMed
phosphatidylinositol-mediated signaling	IEA Inferred from Electronic Annotation more info
regulation of protein secretion	IEA Inferred from Electronic Annotation more info
response to leucine	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info
late endosome	IDA Inferred from Direct Assay more info	PubMed
midbody	IDA Inferred from Direct Assay more info
phosphatidylinositol 3-kinase complex	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: phosphatidylinositol 3-kinase catalytic subunit type 3

Names: phosphatidylinositol 3-kinase catalytic subunit type 3; PI3K type 3; PI3-kinase type 3; PtdIns-3-kinase type 3; phosphatidylinositol 3-kinase p100 subunit

NP_002638.2

EC 2.7.1.137

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002647.2 → NP_002638.2 phosphatidylinositol 3-kinase catalytic subunit type 3

Status: VALIDATED

Source sequence(s)

AK090567, BC053651, BI562123, CA945171

Consensus CDS

CCDS11920.1

UniProtKB/Swiss-Prot

Q8NEB9

Related

ENSP00000262039, OTTHUMP00000163416, ENST00000262039, OTTHUMT00000255804

Conserved Domains (5) summary

cd00870
Location:283 – 412
Blast Score: 469

PI3Ka_III; Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III ...

cd00896
Location:539 – 885
Blast Score: 1562

PI3Kc_III; Phosphoinositide 3-kinase (PI3K), class III, catalytic domain; The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), ...

cd08397
Location:26 – 186
Blast Score: 688

C2_PI3K_class_III; C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks)

smart00146
Location:633 – 835
Blast Score: 570

PI3Kc; Phosphoinositide 3-kinase, catalytic domain

cl00271
Location:467 – 503
Blast Score: 136

PI3Ka; Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000018.9 Reference GRCh37.p5 Primary Assembly

Range

39535199..39661448

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000150.1 Alternate HuRef

Range

36394067..36520574

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC087683.5 (32799..159048)	None
genomic	CH471088.1	EAX01426.1
mRNA	AK022653.1	None
mRNA	AK090567.1	None
mRNA	AK298517.1	BAG60721.1
mRNA	AK308364.1	None
mRNA	BC010388.1	None
mRNA	BC033004.2	AAH33004.1
mRNA	BC053651.1	AAH53651.1
mRNA	BI562123.1	None
mRNA	CA945171.1	None
mRNA	Z46973.1	CAA87094.1
other-genetic	DQ890552.2	ABM92169.1
other-genetic	DQ893712.2	ABM84638.1